Comparison of outcomes for double fenestrated endovascular aneurysm repair versus triple or quadruple fenestrated endovascular aneurysm repair in the treatment of complex abdominal aortic aneurysms.

OBJECTIVE: This study compared outcomes of standard fenestrated endovascular aneurysm repair (St-FEVAR) with renal artery fenestrations only with more complex FEVAR (Co-FEVAR) with additional fenestrations for the superior mesenteric artery or the celiac trunk, or both. METHODS: All consecutive patients treated with FEVAR for short-necked, juxtarenal, or suprarenal aortic aneurysms between January 2010 and July 2016 were included. Patients with stent grafts with a combination of fenestrations and branches were excluded. Data were collected prospectively. All stent grafts used were customized based on the Zenith system (William A. Cook Australia, Ltd, Brisbane, Queensland, Australia). RESULTS: A total of 384 patients (345 men; mean age, 72.7 ± 7.8 years) were treated. St-FEVAR was used in 199 patients (51.8%) and Co-FEVAR in 185 (48.2%), including 30 patients with a quadruple FEVAR. Overall technical success was 373 of 384 (97.1%), and the difference between the St-FEVAR group (195 of 199 [98%]) and the Co-FEVAR group (178 of 185 [96.2%]) was not statistically significant (P = .37). Mean operative time was 135 ± 46 minutes for St-FEVAR and 176 ± 53 minutes for Co-FEVAR (P < .001). Mean fluoroscopy time was 45 ± 17 minutes for St-FEVAR and 57 ± 21 minutes for Co-FEVAR (P < .001). Overall 30-day mortality was two of 384 (0.5%), and the difference between the two groups was not statistically significant (St-FEVAR: 1 of 199 [0.5%] vs Co-FEVAR: 1 of 185 [0.5%]; P = 1.0). Major perioperative complications between St-FEVAR group (22 of 199 [11.1%]) and Co-FEVAR group (24 of 185 [13%]) were similar (P = .64). Mean follow-up was 20 ± 17.1 months. Estimated survival at 1 and 3 years was 95% ± 1.7% and 83.4% ± 3.6% for St-FEVAR vs 94% ± 2.4% and 89.4% ± 3.5%, respectively, for Co-FEVAR (P = .96). Estimated freedom from reintervention at 1 and 3 years was 97.9% ± 1.2% and 90.5% ± 3.1% for St-FEVAR vs 95.4% ± 2.0% and 89.1% ± 4.2%, respectively, for Co-FEVAR (P = .5). Estimated target vessel patency at 1 and 3 years was 99.2% ± 0.4% and 98.6.0% ± 0.6% for St-FEVAR vs 98.6% ± 0.6% and 97.9% ± 0.9%, respectively, for Co-FEVAR (P = .48). CONCLUSIONS: Co-FEVAR is not associated with an increase in perioperative mortality and morbidity compared with St-FEVAR. Co-FEVAR requires longer procedure and fluoroscopy duration, but technical success rates are as high as in St-FEVAR. A liberal use of Co-FEVAR is therefore justified whenever a longer and higher proximal sealing zone is needed.

Spinal cord ischemia after endovascular repair of thoracoabdominal aortic aneurysms with fenestrated and branched stent grafts.

OBJECTIVE: The aim of this study was to report the incidence and associated risk factors of perioperative spinal cord ischemia (SCI) after endovascular repair of thoracoabdominal aortic aneurysms (TAAAs) with fenestrated and branched stent grafts. METHODS: The study included consecutive patients with TAAA treated with fenestrated and branched stent grafts within the period January 2004 to December 2014. Suprarenal abdominal aortic aneurysms treated with fenestrated and branched grafts, even if including all four visceral vessels, were excluded. Patients who died within 30 days after the procedure were excluded from the analysis for SCI. All data were collected prospectively. RESULTS: A total of 218 patients (167 men; mean age, 68.8 ± 7.5 years) were treated. Thirty-day mortality was 17 patients (7.8%). TAAA distribution among the 201 surviving patients was as follows: type I, n = 17 (8.5%); type II, n = 55 (27.4%); type III, n = 63 (31.3%); type IV, n = 54 (26.9%); and type V, n = 12 (5.9%). In the surviving patients, 21 (10.4%) developed perioperative SCI. At 30 days postoperatively, 13 (6.5%) of those patients had transient lower limb weakness, 5 patients (2.5%) had persistent lower limb weakness requiring assistance to stand or to walk, and 3 patients (1.5%) had persistent paraplegia. Five of the 21 patients awoke from anesthesia with a neurologic deficit. The remaining 16 patients had a later postoperative onset of SCI, with the majority of them (14 of 16) within 72 hours after the operation. Multivariate analysis using logistic regression identified operation time >300 minutes (odds ratio [OR], 7.4; 95% confidence interval [CI], 2.6-21.1; P < .001), peripheral arterial disease (OR, 6.6; 95% CI, 2-21.9; P = .002), and baseline renal insufficiency (glomerular filtration rate <30 mL/min; OR, 4.1; 95% CI, 1.1-16.1; P = .04) as independent risk factors for SCI. CONCLUSIONS: In our experience, most SCI events after endovascular TAAA repair are transient, with persistent paraplegia being rare. Patients with prolonged procedure duration, peripheral arterial disease, and baseline renal insufficiency appear to be at higher risk for development of SCI after endovascular TAAA repair.

Retrograde Target Vessel Catheterization as a Salvage Procedure in Fenestrated/Branched Endografting.

PURPOSE: To present retrograde target vessel catheterization as a bailout technique in fenestrated and branched endografting (F/B-EVAR). METHODS: Between November 2003 and November 2014, 11 (1.6%) of 671 consecutive patients with juxtarenal, suprarenal, and thoracoabdominal aortic aneurysms required retrograde target vessel access as a bailout measure during F/B-EVAR due to failure of an antegrade approach. The target vessels involved the left renal artery (LRA) in 6 patients, the celiac artery (CA) in 3 patients, the right renal artery (RRA) in 1 patient, and both renal arteries in 1 patient. RESULTS: The target vessels were successfully catheterized and secured with stent-grafts in 10 patients; a single case was unsuccessful because the fenestration was in the wrong position and blocked against the arterial wall. One (9.1%) patient died within 30 days. Major perioperative complications occurred in 6 patients, including 3 with renal function deterioration, 2 with access-site wound dehiscence, and a case of pneumonia. Median hospital stay was 20 days (range 7-60) and median intensive care unit stay was 2.5 days (range 0-9). Over a mean 26-month follow-up (range 1-60), one unrelated death occurred. Reintervention was required in 1 patient due to progression of an aneurysm of the right iliac artery. CONCLUSION: Retrograde target vessel access in F/B-EVAR is a feasible bailout procedure when antegrade cannulation fails. Secondary technical success is high, but the procedure is associated with higher perioperative morbidity and longer hospital stay.

Early follow-up after endovascular aneurysm repair: is the first postoperative computed tomographic angiography scan necessary?

PURPOSE: To examine whether initial postoperative computed tomographic angiography (CTA) is needed in all patients undergoing endovascular aneurysm repair (EVAR). METHODS: A total of 105 consecutive patients underwent EVAR with standard infrarenal devices in our department between November 2009 and May 2011. Five patients were excluded due to severe renal insufficiency, leaving 100 (85 men; median age 73 years, range 46-91) eligible for prospective enrollment in a triple-modality early postoperative follow-up protocol [intraoperative completion angiography, postoperative duplex ultrasonography (DUS), and plain abdominal radiography). Findings were compared for sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) against the first postoperative CTA results for the detection of endoleaks or other signs of EVAR failure. RESULTS: There were 10 inconclusive DUS examinations. In the remaining 90 patients, DUS had 75.0% sensitivity, 95.4% specificity, 85.7% PPV, and 91.5% NPV for the detection of endoleaks. The intraoperative angiogram, DUS, and abdominal radiograph combined resulted in 87.5% sensitivity and 95.4% specificity, with a 65.6% PPV and 94.8% NPV for the detection of endoleaks. In 2 patients who required a reintervention for endoleak in the early postoperative period, both endoleaks were correctly detected by the triple-modality early postoperative follow-up protocol. CONCLUSION: An early follow-up protocol consisting of an intraoperative completion angiogram, DUS, and abdominal radiograph shows a high sensitivity and NPV for the detection of endoleaks and should detect early migration or kinking of the stent-graft. An initial postoperative CTA is not necessary for most patients undergoing EVAR and should be reserved for those individuals in whom the aforementioned modalities are inconclusive or show signs of endoleak or other EVAR failure.

Fenestrated and branched stent-grafts to treat post-dissection chronic aortic aneurysms after initial treatment in the acute setting.

PURPOSE: To present our initial experience treating post-dissection thoracoabdominal aneurysms with fenestrated and branched grafts. METHODS: Six patients (all men; mean age 62 years, range 44-71) with post-dissection thoracoabdominal aortic aneurysms were selected for treatment with fenestrated and branched grafts. All patients were initially treated with open surgery or endovascular treatment for their acute dissection. In total, 21 visceral arteries were targeted (3 celiac arteries, 6 superior mesenteric arteries, 12 renal arteries). RESULTS: Technical success was achieved in all cases, with no mortality or paraplegia. At completion angiography, all target vessels were patent, and no type I endoleak was seen. A type II endoleak was present in 4 patients, with the false lumen still partially perfused. During follow-up (mean 9 months, range 3-15), no patients died. One targeted renal artery occluded at 1 month. One type Ib endoleak in a left renal artery was successfully treated with additional stenting. Five of the 6 patients had a 6-month follow-up. On abdominal ultrasound, 3 type II endoleaks were still seen. In 2 of these patients, the endoleak was resolved, the false lumen was completely thrombosed, and the maximum aortic diameter had regressed on the 1-year CTA. CONCLUSION: Although longer follow-up results are needed, treatment with fenestrated and branched stent-grafts seems feasible and may be a promising option for the treatment of chronic post-dissection aortic aneurysms.

Infection of honey bees with acute bee paralysis virus does not trigger humoral or cellular immune responses.

We have studied the responses of honey bees at different life stages (Apis mellifera) to controlled infection with acute bee paralysis virus and have identified the haemolymph of infected larvae and adult worker bees as the compartment where massive propagation of ABPV occurs. Insects respond with a broad spectrum of induced innate immune reactions to bacterial infections, whereas defence mechanisms based on RNA interference play a major role in antiviral immunity. In this study, we have determined that honey bee larvae and adult workers do not produce a humoral immune reaction upon artificial infection with ABPV, in contrast to control individuals challenged with Escherichia coli. ABPV-infected bees produced neither elevated levels of specific antimicrobial peptides (AMPs), such as hymenoptaecin and defensin, nor any general antimicrobial activity, as revealed by inhibition-zone assays. Additionally, adult bees did not generate melanised nodules upon ABPV infection, an important cellular immune function activated by bacteria and viruses in some insects. Challenge of bees with both ABPV and E. coli showed that innate humoral and cellular immune reactions are induced in mixed infections, albeit at a reduced level.

Preliminary embolization of the hypogastric artery to expand the applicability of endovascular aneurysm repair.

PURPOSE: To evaluate the efficacy and safety of preliminary hypogastric artery (HA) embolization prior to endovascular aneurysm repair (EVAR). METHODS: A retrospective review was conducted of all 101 consecutive patients (91 men; mean age 73.4 ± 8.7 years) who underwent preliminary embolization of 133 HAs ∼4 to 6 weeks prior to EVAR from January 2005 to August 2009. Fourteen patients with 19 HAs were treated using coils, while 87 patients were treated with Amplatzer Vascular Plugs (AVP) in 114 HAs. All the patients were evaluated before discharge; at 1, 3, and 6 months; and annually thereafter to evaluate the clinical symptoms, potential endoleaks, and the aneurysm size. RESULTS: In the coil group, complete occlusion was achieved in 16 (84.2%) of 19 procedures. There were no acute pelvic ischemic symptoms after HA embolization or EVAR. Five (35.7%) patients had buttock claudication and 2 (16.7%) of 12 men experienced new erectile dysfunction after embolization. At a mean 42.2-month follow-up (range 14-58), 3 (21.4%) patients had a type II leak via retrograde flow in the HA without aneurysm growth and were under observation. In the AVP group, all 114 HAs in 87 patients were successfully occluded; there was no device dislodgment or acute pelvic or limb ischemia observed. Buttock claudication and new sexual dysfunction developed in 12 (13.8%) patients and 4 (5.1%) of 79 men after the procedure, respectively. During a mean 26.4-month follow-up (range 4-54), 2 (2.3%) patients developed distal type I endoleaks after EVAR, but angiography confirmed that neither of the endoleaks was related to the vessel embolized with the AVP. Comparing the outcomes of the treatment groups, the AVP was placed with fewer intraoperative complications (p = 0.013) and more complete occlusion (p = 0.01) than coil embolization. The rate of buttock claudication was lower in the AVP group (p = 0.042). CONCLUSION: Hypogastric artery embolization prior to EVAR is safe and effective. In our experience, the AVP affords easier and more precise placement and provides more complete occlusion, with fewer intraoperative and postoperative ischemic complications than coil embolization.

Paenibacillus larvae Bacteremia in injection drug users.

Paenibacillus larvae causes American foulbrood in honey bees. We describe P. larvae bacteremia in 5 injection drug users who had self-injected honey-prepared methadone proven to contain P. larvae spores. That such preparations may be contaminated with spores of this organism is not well known among pharmacists, physicians, and addicts.

Winter losses of honeybee colonies (Hymenoptera: Apidae): the role of infestations with Aethina tumida (Coleoptera: Nitidulidae) and Varroa destructor (Parasitiformes: Varroidae).

Multiple infections of managed honeybee, Apis mellifera, colonies are inevitable due to the ubiquitous ectoparasitic mite Varroa destructor and might be an underlying cause of winter losses. Here we investigated the role of adult small hive beetles, Aethina tumida, alone and in combination with V. destructor for winter losses and for infections with the microsporidian endoparasite Nosema ceranae. We found no significant influence of A. tumida and V. destructor alone or in combination on the numbers of N. ceranae spores. Likewise, A. tumida alone had no significant effects on winter losses, which is most likely due to the observed high winter mortality of the adult beetles. Therefore, our data suggest that A. tumida is unlikely to contribute to losses of overwintering honeybee colonies. However, high losses occurred in all groups highly infested with V. destructor, supporting the central role of the mite for colony losses.

A novel transfecting peptide comprising a tetrameric nuclear localization sequence.

The transport of exogenous DNA into the nucleus of eukaryotic cells is a prerequisite for successful gene delivery. To favor nuclear transport we synthesized a tetramer of the nuclear localization signal (NLS) of the SV40 large T-antigen as a novel nonviral gene delivery vector. This 4.4-kDa lysine-rich peptide (NLSV404) binds and compacts DNA by electrostatic interaction and forms stable polyplexes. Apart from its sequence-specific potency to mediate nuclear accumulation of conjugated albumin, NLSV404 also displays properties of nuclear transport for plasmid DNA as confirmed by fluorescence in situ hybridization. Further, NLSV404 polyplexes are shown to efficiently transfect various cell lines such as 16HBE14o-, HeLa S6, and Cos7 cells. NLSV404 polyplexes displayed at least 20-fold higher transfection rates than analogous polyplexes formed by the nuclear transport-deficient mutant sequence cNLS. Using growth-arrested cells, NLSV404 complexes were at least 100-fold more efficient than cNLS complexes. Combination of NLSV404 peptide but not of cNLS peptide with preformed polyethylenimine and dendrimer DNA complexes resulted in a strong increase in transfection efficiency. Incubation of cells prior to transfection with NLSV404 polyplexes with excess free peptide NLSV404 but not with cNLS resulted in a dose-dependent dramatic decrease in the transfection rate, suggesting a sequence-specific competitive inhibition. These results indicate that NLSV404 mediates nuclear accumulation of transfected plasmid DNA and that it can be a highly useful component of nonviral gene vectors.

Endovascular management of chronic post-dissection aneurysms.

Open repair is still the gold standard in acute type A dissection. Endovascular repair is advocated for complicated acute type B dissections. Recent evidence also supports the role of endovascular repair in a larger proportion of uncomplicated acute type B dissections. The role of endovascular repair in chronic post-dissection aneurysms, however, is still unclear. Most commonly, post-dissection aneurysms involve the thoracoabdominal aorta, making the use of fenestrated/branched stent-grafts to achieve complete aneurysm exclusion mandatory. These fenestrated/branched stent-grafts have been used with success in atherosclerotic thoracoabdominal aortic aneurysms (TAAAs). In chronic post-dissection aneurysms, however, additional technical challenges arise. The usually narrow true lumen makes the use of branches more tedious and overall planning difficult. A second technical challenge relates to the fact that visceral branches can also originate from the false lumen. In such cases, perforation of the stiff chronic dissection flap is required to obtain access to the vessel. During the period January 2010 to November 2013, 17 patients (13 males, mean age 65±7.8 years) with chronic thoracoabdominal aneurismal degeneration following acute dissection were treated in our department with the use of fenestrated/branched stent-grafts. Technical success was achieved in all cases (100%). Perioperative mortality was two (11.8%) patients. One patient died due to multiple organ failure and one due to cardiac failure. No case of paraplegia was observed. During a 12-month median follow-up (range, 4-28 months) no aneurysm-related deaths were observed. Reintervention was required in three cases to repair a type Ib endoleak from a side branch. Endovascular treatment with fenestrated/branched stent-grafts is feasible for chronic post-dissection aneurysms. Standard thoracic stent-grafting is an option in a minority of patients, when the aneurysm is limited to the thoracic segment. Fenestrated and branched devices can successfully be used for aneurysms extending to the thoracoabdominal aorta.

Inactivation of a non-enveloped RNA virus by artificial ribonucleases: honey bees and acute bee paralysis virus as a new experimental model for in vivo antiviral activity assessment.

RNA-containing viruses represent a global threat to the health and wellbeing of humans and animals. Hence, the discovery of new approaches for the design of novel vaccines and antiviral compounds attains high attention. Here we describe the potential of artificial ribonucleases (aRNases), low molecular weight compounds capable to cleave phosphodiester bonds in RNA under mild conditions, to act as antiviral compounds via destroying the genome of non-enveloped RNA viruses, and the potential of utilizing honey bee larvae and adult bees (Apis mellifera) as a novel experimental system for the screening of new antiviral compounds. Pre-incubation of an Acute bee paralysis virus (ABPV) suspension with aRNases D3-12, K-D-1 or Dp12F6 in a concentration-dependent manner increased the survival rate of bee larvae and adult bees subsequently infected with these preparations, whereas incubation of the virus with aRNases ABL3C3 or L2-3 had no effect at all. The results of RT-PCR analysis of viral RNA isolated from aRNase-treated virus particles confirmed that virus inactivation occurs via degradation of viral genomic RNA: dose-dependent inactivation of ABPV correlates well with the cleavage of viral RNA. Electron microscopy analysis revealed that the morphology of ABPV particles inactivated by aRNases remains unaffected as compared to control virus preparations. Altogether the obtained results clearly demonstrate the potential of aRNases as a new virus inactivation agents and bee larvae/ABPV as a new in vivo system for the screening of antiviral compounds.

Development of a multiplex RT-PCR for the simultaneous detection of three viruses of the honeybee (Apis mellifera L.): acute bee paralysis virus, Black queen cell virus and Sacbrood virus.

A single-step multiple-target (multiplex) reverse transcription-PCR (RT-PCR) was developed for the simultaneous detection and differentiation of three economically important viruses of the honeybee Apis mellifera L.: Acute bee paralysis virus (ABPV), Black queen cell virus (BQCV) and Sacbrood virus (SBV). Three compatible sets of primers, specific for each virus, were designed in conserved regions of the viral genomes for use in a one-step (single tube) RT-PCR assay. The individual RT-PCR assays and the combined multiplex assay were optimized for highest sensitivity and specificity. The multiplex RT-PCR assay was tested on field samples collected from Austrian honeybee colonies. All three viruses were detected, and their identity was confirmed by sequencing of the PCR products. The described multiplex RT-PCR proved to be an accurate tool for rapid simultaneous detection of ABPV, BQCV and SBV directly in honeybee specimens.

Phylogenetic analysis of deformed wing virus genotypes from diverse geographic origins indicates recent global distribution of the virus.

Honeybees originating from 10 different countries (Austria, Poland, Germany, Hungary, Slovenia, Nepal, Sri Lanka, the United Arab Emirates, Canada, and New Zealand) located on four continents were analyzed for the presence of deformed wing virus (DWV) nucleic acid by reverse transcription-PCR. Two target regions within the DWV genome were selected for PCR amplification and subsequent sequencing, i.e., a region within the putative VP2 and VP4 structural-protein genes and a region within the RNA helicase enzyme gene. DWV nucleic acid was amplified from 34 honeybee samples representing all the above-mentioned countries with the notable exception of New Zealand. The amplification products were sequenced, and phylogenetic analyses of both genomic regions were performed independently. The phylogenetic analyses included all sequences determined in this study as well as previously published DWV sequences and the sequences of two closely related viruses, Kakugo virus (KGV) and Varroa destructor virus 1 (VDV-1). In the sequenced regions, the DWV genome turned out to be highly conserved, independent of the geographic origins of the honeybee samples: the partial sequences exhibited 98 to 99% nucleotide sequence identity. Substitutions were most frequently observed at the same positions in the various DWV sequences. Due to the high level of sequence conservation, no significant clustering of the samples in the phylogenetic trees could be identified. On the other hand, the phylogenetic analyses support a genetic segregation of KGV and VDV-1 from DWV.

Aortocaval fistula after stent-graft repair.

PURPOSE: To report an aortocaval fistula after stent-graft repair and the feasibility of interventional treatment. CASE REPORT: A 78-year-old man with a 61-mm infrarenal aortic aneurysm (AA) was treated successfully with a Zenith bifurcated stent-graft. Three years later, the patient presented with deteriorating renal function and acute bronchial obstruction. Computed tomography showed an aortic diameter increased to 90 mm, dilatation of the inferior vena cava, and a distal type I endoleak. The patient's condition quickly deteriorated, and emergent imaging found a fistula with brisk flow between the aneurysm sac and the left iliac vein within a distal type I endoleak. During emergency endovascular repair, iliac extensions were implanted in the right common iliac artery and left external iliac artery. The left hypogastric artery was coil embolized to exclude flow into the aneurysm sac. After positioning the extensions, cardiac function improved, and the fistula was no longer palpable. The cardiac indices and renal function normalized, and he was discharged 20 days after admission. CONCLUSION: Aortocaval fistulas are a rare complication of AA stent-graft repair and may be successfully treated by interventional means.

Phylogenetic analysis of acute bee paralysis virus strains.

Reverse transcription-PCR assays have been established for a quick, sensitive, and specific diagnosis of acute bee paralysis virus (ABPV), a common virus of the honeybee (Apis mellifera), directly from clinical samples. A 3,071-nucleotide fragment of the ABPV genome, which includes the entire capsid polyprotein gene, was amplified from Austrian, German, Polish, and Hungarian ABPV samples and sequenced, and the sequences were compared. The alignment of a smaller fragment with ABPV sequences from the United States and the United Kingdom revealed nucleotide identity rates between 89 and 96%, respectively. Phylogenetic trees which display the molecular relationship between the viruses of different geographic origin were constructed.